With an increase in the industrial and medical use of radiation, various studies on the effects of radiation on the human body have been conducted, and particularly, cancer therapy with radiation has received attention. It is known that high doses of ionizing radiation cause DNA damage, genetic modification, and diseases, including cancer, but a radiation dose of 200 mGy or less and a radiation dose rate of 6 mGy/hr or less inhibit cancer development by activating immune responses.
In general, studies on the relationship between radiation and cancer development, particularly gene responses to radiation, have been conducted, but confounding factors have significantly affected the results to reduce the reliability of the results. However, most studies conducted to date could not explain various responses, which occur in the cells, tissues and organs of the body in the body stage, because these studies were performed using gene-modified cell lines or cancer cell lines. In other words, because gene responses were evaluated using general mice, a variety of genes were expressed, and because cancer development was not limited to a specific organ, it was difficult to analyze gene responses.
In prior art methods that use cells for cancer research, genes were modified, or cancer cells lacking p53 that is important in cancer development were irradiated. For this reason, there was a problem in that the results could not be applied to individuals, because they did fundamentally differ from the responses of normal cells. To overcome this problem, studies on the effects of radiation on cancer development have been conducted using mice having a gene similarity of 95% or more with humans. However, cancer incidence in general mice is very low, and thus a variety of mouse models for cancer research have been used.
In prior studies, a variety of methods were used to screen genes sensitive to a low level (0.7 mGy/hr) of radiation. However, genes disclosed in the present invention are not yet known as genes sensitive to a low level (0.7 mGy/hr) of radiation. Technologies prior to the identification of the profile of genes according to the present invention are as follows.
(1) Radiation-sensitive genes were identified in human breast epithelial cells using a gene probe method (Malone J, Ullrich R (2007) Radiat Res 167: 176-1847).
(2) Genes sensitive to early radiation were found in irradiated human lymphocytes using microarray analysis and a quantitative nucleic acid amplification technique (Turtoi A et. al. (2008) Int J Radiat Biol 84: 375-387).
(3) Biological dose markers were identified in male BALB/c, irradiated with 1-7 Gy, by blood protein analysis (Ossetrova N I, Blakely W F (2009) Int J Radiat Biol 85: 837-850).
(5) A network of 10 herb genes including c-Jun, HDAC1, RELA (p65 subunit of NFKB), PKC-beta, SUMO-1, c-Abl, STAT1, AR, CDK1 and IRF1 was identified by linear regression analysis of 500 genes that represent a biological network (Eschrich S et. al. (2009) Int J Radiat Oncol Biol Phys 75: 497-505).
(5) Single nucleotide polymorphism markers enabling the prediction of response to radiation were identified in 277 human lymphocyte cell lines (Niu N et. al. (2010) Genome Res 20: 1482-1492).
(6) A recent study provided a new overview of response to radiation using EPI-200 that is a three-dimensional tissue model mimicking human epidermal tissue (Mezentsev A, Amundson S A (2011) Radiat Res 175: 677-688).
(7) An RNA-based expression analysis method was used as a tool for biological dose evaluation in the measurement of radiation exposure and toxicity (Pogosova-Agadjanyan E L et. al. (2011) Radiat Res 175: 172-184).
(8) Radiation-sensitive genes were identified in human lymphocytes and leucocytes using multiplex quantitative nucleic acid amplification and a method for analysis of a specific gene (Kabacik S et. al. (2011) Int J Radiat Biol 87: 115-129).
Accordingly, the present inventors have made efforts to find genes showing a sensitive response to a low level of ionizing radiation. As a result, the present inventors have analyzed the functions of 7 genes playing an important role in immunity (Ighg, Saa2, Defb6, Reg3g, Tac2 and Igh-VJ558) and apoptosis (Klk1b27), and have found that the seven genes have not been reported, thereby completing the present invention.